Lipid modifications of cells molecule and Lipid signaling,

Lipid-Mediated Localization of Signaling Proteins

Protein Lipidation

 N-myristoylation

 Prenylation

 S-Palmitoylation
N-myristoylation

Myristic acid (tetradecanoic acid) 14:0

saturated fatty acid
molecular formula CH3(CH2)12COOH
N-myristoylation

Methionylpeptidase
N-MYRISTOYLATION
Prenylation
• Farnesylation
• Geranylgeranylation

C15

C20
Prenylation
FARNESYLATION
S-Palmitoylation
S-Palmitoylation
S-Palmitoylation
Lipid raft

1. Non-raft membrane
2. Lipid raft
3. Lipid raft associated transmembrane protein
4. Non-raft membrane protein
5. Glycosylation modifications (on glycoproteins and glycolipids)
6. GPI-anchored protein
7. Cholesterol
8. Glycolipid
Lipid Raft
 Contain twice the amount of cholesterol

 Enriched in sphingolipids such as sphingomyelin

 Phosphatidylcholine levels are decreased

 The hydrophobic chains of the lipids contained in the rafts are more saturated
and tightly packed than the surrounding bilayer.

 Cholesterol is the dynamic "glue" that holds the raft together.

 Lipid rafts more rigid and in a less fluid state.

 Detergent resistance
IgE signaling
APC signaling
EGF signaling

EGF receptor (ErbB1), HER2/neu (ErbB2),

ErbB3, and ErbB4.
 EGF receptor is present in flattened, low-density lipid rafts that lack
caveolin-1

 Association of the EGF receptor with lipid rafts is readily reversible

 EGF receptor, which has never been shown to acquireany such

posttranslational lipid modifications

 60-amino-acid segment in the most membrane-proximal region of the

extracellular domain of the EGF receptor is responsible for targeting
the receptor to lipid rafts

 Some pathways are stimulated only through EGF receptors residing in

lipid rafts, while other pathwaysare stimulated only when the EGF receptors
exit caveolae/lipid rafts.
PDK1 in Activating AGC Protein Kinase
Phosphatidylinositol phosphorylation
Plekstrin Homology domain (PH domain)
Arachidonic acid (AA, sometimes ARA)
omega-6 fatty acid 20:4(ω-6).
Voltage gatted Ca channel
CRAC (SOC) channel
ARC (Arachidonic Acid Regulated Calcium Channel)

Activation of ARC by 8 uM stimulation of Arachidonic acid

ARC regulation

 ARC channels is inhibited by a calcineurin-mediated

dephosphorylation

 Dependent on protein kinase A (PKA) activity.

 Dependent on AKAP79, a protein which scaffolds both PKA and

calcineurin
Obviously, the study of ARC channels is still
only in its infancy and much remains to be
discovered about their properties,regulation,
and functions.
To be continued